DESCRIPTION: (Applicant's Abstract) Chronic pain affects nearly 70 million people a year in the United States and costs billions of dollars in medical treatments and lost productivity. To date, all investigations concerning the blood-brain barrier and opioid entry into the brain have been performed on naive, non-pained rats. The focus of my research will be to build upon already existing and proven research methodologies by introducing a pathological state (i.e. chronic pain) and then examining opioid peptide delivery across the BBB as well as determine what other BBB mechanisms are altered during pain. This study will be the first of its kind to examine the role that BBB plays in opioid transport and distribution during pain. A superior model to those used previously in assessing opioid delivery to the brain, since opioid analgesics are typically administered in an effort to relieve pain. The hypothesis of this study is that mediators released during pain affect the biochemical and molecular structure of the blood-brain barrier, resulting in alterations of opioid peptide transport into the brain. These studies will provide new information about mechanisms that may contribute to the permeability changes observed during chronic pain states. Ultimately, this grant may identify a pharmacological approach that could be used in conjunction with current therapies to alleviate pain with greater efficacy and fewer adverse side effects.